Improved Synthetic Route to Heteroleptic Alkylphosphine Oxides

A new method for the synthesis of heteroleptic alkylphosphine oxides (R₂R¹PO, where R ≠ R¹) from secondary phosphine oxides (or SPOs, R₂HPO) is presented. These reactions were fast at room temperature, sterically selective, high yielding, and >95% pure after an aqueous wash. Deprotonation of an SPO generates a phosphinite anion ([R₂P–O]⁻) that was found to be highly selective for nucleophilic P–C bond formation (as opposed to O–C bond formation) with alkyl halides. Surprisingly, most strong organometallic bases failed to deprotonate SPOs to their respective phosphinite anions (p<i>K</i>_as for most SPOs are <27). Only sodium bis­(trimethylsilyl)­amide (NaHMDS) cleanly formed the phosphinite anion, which was stable in solution (0.1 M, 23 °C in THF) for over 24 h. The need for a very specific base to deprotonate suggests that both ion pairing and the conjugate acid play a role in stabilizing the phosphinite anion. Phosphinite anion reactivity followed the expected trend for an S_N2 mechanism on reaction with alkyl halides; elimination products were never observed. A wide variety of heteroleptic alkylphosphine oxides were isolated in near-quantitative yield with only an aqueous wash as purification. This methodology was then used to make new bis­(phosphine oxide)­alkanes and unsymmetrical α,ω-bis­(phosphine oxide)­alkanes (R₂P­(O)­(CH₂)₃P­(O)­R¹₂) on the benchtop with unprecedented ease

A Bright Fluorescent Probe for H₂S Enables Analyte-Responsive, 3D Imaging in Live Zebrafish Using Light Sheet Fluorescence Microscopy

Hydrogen sulfide (H₂S) is a critical gaseous signaling molecule emerging at the center of a rich field of chemical and biological research. As our understanding of the complexity of physiological H₂S in signaling pathways evolves, advanced chemical and technological investigative tools are required to make sense of this interconnectivity. Toward this goal, we have developed an azide-functionalized <i>O</i>-methylrhodol fluorophore, <b>MeRho-Az</b>, which exhibits a rapid >1000-fold fluorescence response when treated with H₂S, is selective for H₂S over other biological analytes, and has a detection limit of 86 nM. Additionally, the <b>MeRho-Az</b> scaffold is less susceptible to photoactivation than other commonly used azide-based systems, increasing its potential application in imaging experiments. To demonstrate the efficacy of this probe for H₂S detection, we demonstrate the ability of <b>MeRho-Az</b> to detect differences in H₂S levels in C6 cells and those treated with AOAA, a common inhibitor of enzymatic H₂S synthesis. Expanding the use of <b>MeRho-Az</b> to complex and heterogeneous biological settings, we used <b>MeRho-Az</b> in combination with light sheet fluorescence microscopy (LSFM) to visualize H₂S in the intestinal tract of live zebrafish. This application provides the first demonstration of analyte-responsive 3D imaging with LSFM, highlighting the utility of combining new probes and live imaging methods for investigating chemical signaling in complex multicellular systems

Synthesis and Electronic Properties of Oxidized Benzo[1,2‑<i>b</i>:4,5‑<i>b</i>′]dithiophenes

Benzo­[1,2-<i>b</i>:4,5-<i>b</i>′]­dithiophenes were oxidized under mild conditions with <i>m</i>-CPBA to yield the corresponding bis-sulfones (or tetraoxides). These sulfones possess red-shifted absorption and emission spectra relative to the parent molecules. Electrochemical analyses reveal that the benzodithiophene molecules are transformed from electron donors to electron acceptors

Synthesis and Electronic Properties of Oxidized Benzo[1,2‑<i>b</i>:4,5‑<i>b</i>′]dithiophenes

Benzo­[1,2-<i>b</i>:4,5-<i>b</i>′]­dithiophenes were oxidized under mild conditions with <i>m</i>-CPBA to yield the corresponding bis-sulfones (or tetraoxides). These sulfones possess red-shifted absorption and emission spectra relative to the parent molecules. Electrochemical analyses reveal that the benzodithiophene molecules are transformed from electron donors to electron acceptors

A Bright Fluorescent Probe for H₂S Enables Analyte-Responsive, 3D Imaging in Live Zebrafish Using Light Sheet Fluorescence Microscopy

Hydrogen sulfide (H₂S) is a critical gaseous signaling molecule emerging at the center of a rich field of chemical and biological research. As our understanding of the complexity of physiological H₂S in signaling pathways evolves, advanced chemical and technological investigative tools are required to make sense of this interconnectivity. Toward this goal, we have developed an azide-functionalized <i>O</i>-methylrhodol fluorophore, <b>MeRho-Az</b>, which exhibits a rapid >1000-fold fluorescence response when treated with H₂S, is selective for H₂S over other biological analytes, and has a detection limit of 86 nM. Additionally, the <b>MeRho-Az</b> scaffold is less susceptible to photoactivation than other commonly used azide-based systems, increasing its potential application in imaging experiments. To demonstrate the efficacy of this probe for H₂S detection, we demonstrate the ability of <b>MeRho-Az</b> to detect differences in H₂S levels in C6 cells and those treated with AOAA, a common inhibitor of enzymatic H₂S synthesis. Expanding the use of <b>MeRho-Az</b> to complex and heterogeneous biological settings, we used <b>MeRho-Az</b> in combination with light sheet fluorescence microscopy (LSFM) to visualize H₂S in the intestinal tract of live zebrafish. This application provides the first demonstration of analyte-responsive 3D imaging with LSFM, highlighting the utility of combining new probes and live imaging methods for investigating chemical signaling in complex multicellular systems